2021
DOI: 10.1016/j.ygyno.2021.01.025
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Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study

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Cited by 53 publications
(53 citation statements)
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“…We originally hypothesized that the mutations in p53, a well-established controller of the G1/S and G2/M cell cycle checkpoints, would predict for enhanced synergy. This hypothesis follows our recently published translational study of GOG-86P in which patients with mutations in TP53 had significantly improved outcomes when bevacizumab was combined with chemotherapy as compared to other experimental agents [3]. However, the majority of endometrial organoid models used in this study had wild-type (WT) p53 (Figure 2), precluding a definitive analysis of the role of p53 in sensitivity.…”
Section: Discussionsupporting
confidence: 68%
See 1 more Smart Citation
“…We originally hypothesized that the mutations in p53, a well-established controller of the G1/S and G2/M cell cycle checkpoints, would predict for enhanced synergy. This hypothesis follows our recently published translational study of GOG-86P in which patients with mutations in TP53 had significantly improved outcomes when bevacizumab was combined with chemotherapy as compared to other experimental agents [3]. However, the majority of endometrial organoid models used in this study had wild-type (WT) p53 (Figure 2), precluding a definitive analysis of the role of p53 in sensitivity.…”
Section: Discussionsupporting
confidence: 68%
“…Recent progress has been made in defining the molecular biology of endometrial carcinoma, which has led to the use of targeted agents to treat this disease. The addition of targeted therapies including anti-angiogenics in conjunction with chemotherapy may be more effective than chemotherapy alone, as we have recently reported [ 3 ].…”
Section: Introductionmentioning
confidence: 96%
“…There is mounting evidence, including a recent report from the NRG Oncology cooperative group, demonstrating that mutated TP53 predicts response to VEGF pathway inhibitors (VEGFi), including bevacizumab and pazopanib [ 21 23 , 25 , 26 ]. The reason for this relationship appears to be upregulation of the VEGF/VEGFR axis as one of the consequences of TP53 mutations [ 21 23 , 25 , 26 ]. However, we performed a post hoc analysis to determine if eliminating patients matched on the basis of this relationship would impact the study results.…”
Section: Resultsmentioning
confidence: 99%
“…In a post hoc analysis, assessment of TP53 mutation status showed that women with TP53 mutant EC had both improved progression free- and overall survival when treated with bevacizumab and chemotherapy, whereas women with TP53 wild-type tumours showed no difference in outcomes. 63 The authors concluded p53/ TP53 could be used as a biomarker to help predict patients with EC more likely to respond to bevacizumab treatment.…”
Section: P53abn Endometrial Cancermentioning
confidence: 99%